One form of brain tumor, glioma, is the most frequent brain tumor in adults and, in its most malignant forms (astrocytoma grade IV or glioblastoma multiforme), represents some of the most aggressive cancers in man, with a 5-year survival rate of less than 5% (Reardon et al., 2006, J. Clin. Oncol., 24, 1253). Gliomas are classified into subcategories according to their phenotypical resemblance to glial cells, mostly astrocytes (astrocytomas) or oligodendrocytes (oligodendrogliomas). Based on histopathological features, gliomas are also subdivided into low grade (grade I and II) and high grade (grade III and IV) tumors, which have distinct clinical prognoses (Reardon et al., 2006 , supra).
Glioblastoma multiforme (GBM) is a devastating invasive brain tumor able to give rise to many kinds of differentiated tumor cells. GBMs remain one of the most deadly cancers in adults, with an average period between diagnosis and death of ˜12 months. GBM growth and persistence depend on cancer stem cells (Singh et al., 2003, Cancer Res, 63, 5821-5828; Singh et al., 2004, Nature, 432, 396-401) with enhanced DNA damage repair programs (Bao et al., 2006, Nature, 444, 756-760) that also induce recurrence and resist current chemo- and radio-therapies. This discovery provides a plausible explanation for the difficulty of GBM treatment and the high rate of relapse. Indeed, as GBM cells are highly invasive, surgery is not routinely curative. New strategies to target GBM stem cells are thus required. One key pathway implicated in the control of GBM growth and stemness is HH-GLI (Hedgehog-Gli) (Clement et al,. 2007, Curr Biol, 17, 165-172). This role of HH-GLI parallels its control of normal brain growth stem cell behavior (Palma and Ruiz i Altaba, 2004, Development, 131, 337-345). Interestingly, HH-GLI was shown to regulate a number of stemness genes, including NANOG (Stecca and Ruiz i Altaba, 2009, Embo J, 28, 663-676). The expression of the homeobox gene NANOG forms part of an Embryonic Stem (ES)-like stemness signature described in GBMs (Clement et al., 2007 , supra), later also found in other advanced cancer types (Ben-Porath et al., 2008, Nat Genet, 40, 499-507). However, it is not known if this signature in general, and NANOG in particular, have functional relevance in these tumors or their stem cells.
Thus, given the many suggested GLI1 downstream genes, there have not been demonstrated, until now, essential mediators that could provide additional intervention strategies to treat GBMs and other brain tumors and/or cancers.
The invention disclosed in the present application solves this problem by having identified a new target and mediator that has functional relevance in tumors and their cancer stem cells, particularly GBM tumors.